Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 6, 2021; 9(19): 5019-5027
Published online Jul 6, 2021. doi: 10.12998/wjcc.v9.i19.5019
SMAC exhibits anti-tumor effects in ECA109 cells by regulating expression of inhibitor of apoptosis protein family
Ning Jiang, Wei-Quan Zhang, Hong Dong, Ying-Tao Hao, Li-Ming Zhang, Lei Shan, Xiao-Dong Yang, Chuan-Liang Peng
Ning Jiang, Wei-Quan Zhang, Ying-Tao Hao, Li-Ming Zhang, Lei Shan, Xiao-Dong Yang, Chuan-Liang Peng, Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan 250100, Shandong Province, China
Hong Dong, Department of Nursing, The Second Hospital of Shandong University, Jinan 250100, Shandong Province, China
Author contributions: Jiang N and Peng CL designed the study; Zhang WQ wrote the paper; Dong H, Hao YT, and Zhang LM drafted the work and collected the data; Shan L and Yang XD collated and analyzed the data.
Institutional review board statement: The study was reviewed and approved by the Second Hospital of Shandong University Institutional Review Board.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chuan-Liang Peng, MD, Chief Physician, Department of Thoracic Surgery, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Jinan 250100, Shandong Province, China. pechuliang@126.com
Received: March 4, 2021
Peer-review started: March 4, 2021
First decision: April 6, 2021
Revised: April 8, 2021
Accepted: May 19, 2021
Article in press: May 19, 2021
Published online: July 6, 2021
Processing time: 112 Days and 3.7 Hours
ARTICLE HIGHLIGHTS
Research background

The poor prognosis and rising incidence of esophageal cancer highlight the need for improved therapeutics that are essential prior to treatment. LCL161 is an SMAC (second mitochondrial activator of caspases) mimic and inhibitor of apoptosis protein (IAP) antagonist which exhibits anti-tumor effects and improves the chemical sensitivity of many cancers.

Research motivation

In order to improve the chemical sensitivity of esophageal cancer, we studied the effects and mechanisms of the SMAC on esophageal cancer. Our study will provide new ideas for the treatment of esophageal cancer.

Research objectives

The aim of this study was to ascertain the effects and mechanisms of the SMAC analog LCL161 on esophageal cancer cells.

Research methods

MTT assay and TUNEL assay were used to detect cell proliferation and apoptosis, respectively. Western blot analysis was used to study the molecular mechanisms of LCL161-induced death of ECA109 cells.

Research results

LCL161 decreased ECA109 cell proliferation in a dose- and time-dependent manner and induced apoptosis of ECA109 cells in a dose-dependent manner. Also, LCL161 induced a significant decrease in the expression of the XIAP and significant increase in the expression of Caspase-3. In addition, Bax increased significantly with increasing concentrations of LCL161, and the relative expression of Bax was significantly different between groups.

Research conclusions

These findings support the hypothesis that LCL161 can inhibit proliferation and induce apoptosis in esophageal cancer cells by regulating the expression of IAP family, suggesting that it has potential to be an effective treatment for esophageal squamous cell carcinoma (ESCC).

Research perspectives

Our results confirmed that the Smac mimic LCL161 decreased ECA109 cell proliferation in a dose- and time-dependent manner and induced ECA109 cell apoptosis in a dose-dependent manner. Additionally, changes in the apoptotic signals of XIAP, Caspase-3, and Bax provide a theoretical basis for the treatment of ESCC with LCL161. The underlying molecular mechanisms need to be further investigated.